Journal
STEM CELL REPORTS
Volume 10, Issue 1, Pages 180-195Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.11.017
Keywords
-
Categories
Funding
- National Science Fund for Excellent Young Scholars [31725011]
- National Science Fund for Outstanding Young Scholars [31422022]
- National Natural Science Fund [31370980, 81700946]
- Clinical Research Physician Program of Tongji Medical College, HUST
Ask authors/readers for more resources
Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile-SMH patients. Accordingly, SMH was observed in circadian-rhythm-disrupted or BMAL1-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1. Interestingly, in juvenile SMH patients, we observed that MMP3 was obviously increased. Consistently, MMP3 was upregulated during the whole growth period of 3-10 weeks in Bmal1(-/-) mice. Given these findings, we set out to characterize the underlying mechanism and found BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together, our results provide insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available